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Background and Aims: Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker strongly associated with atherosclerotic cardiovascular disease (ASCVD). Our aim was to evaluate the role of NLR on pulse wave velocity (PWV) after adding-on proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i) in familial hypercholesterolemia (FH) subjects with ASCVD.Methods and Results: In this prospective observational study, we evaluated 45 FH subjects with ASCVD on high-intensity statins plus ezetimibe and with an off-target LDL-C. Study population was divided into two groups according to the mean value of NLR. All patients received PCSK9-i therapy and obtained biochemical analysis as well as PWV evaluation at baseline and after six months of PCSK9-i. After six months of add-on PCSK9-i therapy, a significant reduction of TC, LDL-C, Non-HDL-C, Lp(a) and ApoB plasma levels was observed in the two groups; while low-NLR group exhibited a significant PWV reduction after six-month therapy with PCSK9-i (Δ -16.2%, p < 0.05), no significant changes in PWV were observed in the high-NLR group.Conclusions: Only FH subjects with low-NLR experienced a significant reduction of PWV after PCSK9-i. Our findings suggest a role of NLR in predicting PCSK9-i effect in FH subjects with ASCVD. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is characterized by increased cardiovascular risk; despite-high intensity statins, only few patients with FH achieve the recommended low-density lipoprotein cholesterol (LDL-C) targets. We aimed to evaluate the effectiveness of six-month add-on therapy with proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-i) or ezetimibe on lipid profile and pulse wave velocity (PWV) in patients with FH. In this observational study, we evaluated 98 genetically confirmed patients with FH with an LDL-C off-target despite high-intensity statins with or without ezetimibe; of these, 53 patients (statin plus ezetimibe) added PCSK9-i (PCSK9-i group) and 45 (statin only) added ezetimibe (EZE group) per applicable guidelines and reimbursement rules. All patients obtained biochemical analysis and PWV evaluation at baseline and after six months of optimized treatment. After 6 months of add-on therapy, most patients achieving LDL-C targets were in the PCSK9-i group (77.3% PCSK9-i group vs 37.8% EZE group, P <.001). The PCSK9-i group achieved both a greater LDL-C and PWV reduction than the EZE group [−51% vs −22.8%, P <.001 and −15% vs −8.5%, P <.01, respectively]. In a linear regression analysis, we showed a coefficient (r) of 0.334 for the relationship between ΔPWV and ΔLDL (P <.05); moreover, in an exploratory analysis, the relationship appeared to be stronger in patients with FH without cardiovascular events (r = 0.422, P <.01). Lipid and PWV profiles in patients with FH significantly improved after addition of PCSK9-i or ezetimibe to high-intensity statin therapy; moreover, ΔPWV was associated with ΔLDL. Our results are consistent with a beneficial role of these novel therapies in FH subjects. • Despite high-intensity statins, few FH subjects achieve the recommended LDL-C goal. • We investigated the effectiveness of PCSK9-i or ezetimibe in FH subjects. • After 6 months, most patients reaching LDL-C goal were in the PCSK9-i group. • The PCSK9-i group achieved both a greater LDL-C and PWV reduction than the EZE group. • A linear regression analysis showed a relationship between ΔPWV and ΔLDL. [ABSTRACT FROM AUTHOR]

Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leaves and Spartium junceum flowers were tested for cytotoxic effects against glioblastoma U-373 tumour cells. Onopordum acanthium extract was found to be ~5 times more cytotoxic than Spartium junceum (IC50 values of 309 and 1602μg/ml, respectively). Similar to most chemotherapeutic agents killing through the intrinsic pathway, Onopordum killed the cells via apoptosis, which was confirmed by the activation of caspase-3. Spartium exerted its weak cytotoxic effect, presumably by a caspase-independent, non-apoptotic form of necrotic-like programmed cell death. Onopordum acanthium is considered a promising plant for the researchers investigating putative biological activities, particularly antitumour and immune-related activity. [ABSTRACT FROM AUTHOR]